Project Summary/Abstract The knee meniscus, and other fiber-reinforced load-bearing soft tissues, are remarkably strong and durable, however they do become damaged and fail, creating tears, and resulting in pain, impaired function, and, eventually, joint disorders. Therefore, it is crucial to manage meniscus tears in a manner that minimizes further damage and failure and thus osteoarthritis risk. Science-based treatments for meniscus pathology critically require quantifying the mechanisms of meniscus damage and failure and the effects of tears on the rest of the meniscus. However, this has not yet been done. Although the meniscus has undergone decades of tensile loading studies, the accumulation of tissue damage that begins at yield and progresses until failure has not been addressed. We hypothesize that accumulation of tissue damage strongly depends on fascicle microstructure, loading rate, and the presence of a tear. We hypothesize two micro-scale damage mechanisms: (1) inter-fascicle connections stretching, accumulating damage, and failing as fascicles slide past each other (interface damage), and (2) fiber bundles within the fascicles stretching, accumulating damage, and failing (fascicle damage). We also hypothesize that a tear (in engineering terms, crack) disrupts the fascicle microstructure, creating a crack-induced stress concentration that causes premature damage and failure. Despite its significance to meniscus pathology, there is no quantitative prediction of damage accumulation in the meniscus. This study is aimed to address this large and critical gap in knowledge. The objectives of this study are to identify and quantify meniscus tissue damage and failure using a robust multi-scale structural model with strong physical interpretations. We will test hypotheses for interface and fascicle damage mechanisms (Aim 1) and the contribution of a meniscus crack (Aim 2) using a combination of experimental tensile loading to rupture and a model of meniscus tissue damage (Aim 3). This study will provide important new capabilities to predict how and when the meniscus, with and without an initial tear, becomes damaged and fails. The proposed work will provide groundwork for science-based medicine to develop treatments for meniscus pathology. !